The Local Treatment of Acne

There is a good deal of evidence that an essential factor in the pathogenesis of acne is the presence offree fatty acids on the skin and that these fatty acids are produced from sebum triglycerides by the action of lipase derived from Corynebacterium acnes. If this hypothesis isaccepted, then an essential link in the chain of causation of acne is the presence and growth of Corynebacterium acnes (Voss, 1974).

There is a good deal of evidence that an essential factor in the pathogenesis of acne is the presence offree fatty acids on the skin and that these fatty acids are produced from sebum triglycerides by the action of lipase derived from Corynebacterium acnes. If this hypothesis isaccepted, then an essential link in the chain of causation of acne is the presence and growth of Corynebacterium acnes (Voss, 1974).
This organism is by no means invulnerable to the action of antibiotics and antiseptics (Noble et 01., 1974), so that the local application of such substances might be expected to have a notable effect in controlling the bacterial population. In practice , however, the local treatment of acne has proved rather disappointing and certainly does not give results comparable with the systemic (oral) administration of tetracyclines, which presumably work by suppressing bacterial growth.
Although the contents of the pilosebaceous follicle are not as easily examined as the surface lipoids, it is clear that Corynebacterium acnes is present at some depth in the follicleand that the process of lipolysis starts there. If the passage of sebum to the surface is slow, or impeded as in a comedo, a greater bacterial population and a higher concentration of free fatty acid within the follicle can be expected. There is also independent evidence (MacKee et al.• 1945) that absorption of lipid material takes place more readily through the epithelium of the follicular wall than through the skin surface, so that a comparatively modest amount of free fatty acid within thc follicle may have as much irritant effect as a greater concentration on the surface. It seems reasonable therefore to suppose that the relative ineffectiveness of locally applied anti-bacterial agents in the treatment of acne results from the inability of those substances to reach the interior of the follicle in adequate concentration, espccially when this is partly or totally blocked by comedo formation. Although tetracycline has some direct inhibitory action on lipase, this occurs only at rather high concentrations, so that once lipase has been formed inside the follicle it willcontinue to act even on the skin surface in the presence of a concentration of tetracycline which is sufficient to inhibit bacterial growth and the formation of fresh lipase.
An attempt has therefore been made to formulate a local application which combinesa suitable antibacterial and lipase-inhibiting agent with substances having a surface-active and detergent property so as to facilitate penetration and diffusion into the follicular duct.

FORMULATION
In-vitro tests using mixtures of appropriate lipids were made with eleven surfactants and of these the three ethoxylate of lauryl alcohol was selected as the most promising for the solubilisation of the acne plug.
Using a glyceryl trioleate substrate and pancreatic lipase, 28 ethoxylated surfactants were examined for lipase inhibition. Among these. nonyl phenol ethylene oxide condensate (Ethy-Ian BV) showed a high level of lipase inhibition and was selected.
In the choice of an antibacterial agent, particular regard was made to oil/water partition and this was examined in an emulsion in which squalene was used as the lipoid phase. Among nine antiseptics tested, Triclosan (2,4,4', trichloro-2'hydroxydiphenyl ether) showed the highest 0/ W coefficient and was found to have a minimum inhibitory concentration on the growth of Corynebacterium acnes (ATCC 6919) of 1.0 ppm.
As an aid to surface cleansing and to formulation, a further surfactant was incorporated. i.e. a mixture of sodium lauryl ether sulphate (Ernpicol ESB 50) and sodium salts of the sulphosuccinic acid monoester of lauryl alcohol polyglycol ether (Condanol).
These materials were blended so as to form a gel and lightly perfumed. Doctor and patient assessment showed a good agreement, i.e., the state at the time of examination tallied with the patient's statement of his progress over the preceding period.
Both products were found to produce a measure of improvement in the majority of cases. Thus, according to the physician's assessment, improvement was recorded in 76% of patients with the gel and in 68% with the control. 69% of patients recorded an improvement with the gel and 51% with the control. These differences do not achieve statistical significance. The comparison between the two, however, in which the doctor and the patient agreed, showed a preference for gel in 57%, a preference for the control in 18%. and no expressed preference in the remaining 25%, indicating a significant superiority of the gel (P= 0.05). The assessment of the severity of acne and the effects of treatment are difficult to quantify. One of the chief difficulties arises from the day-to-day variability in the disorder so that the condition as seen at the time of a single examination may not truly represent the activity of the disease. For this reason we have paid full attention to the observations of the patient. who sees the lesions daily over a whole period. Further, the patient's own reaction to his acne is a most important part of symptomatology.
In the assessment of a new product a placebo effect has been recorded by many observers, and the present trial was therefore designed as a comparison with anotherapplication. the effects of which were already reasonably well known. For the control we chose Phisohex, a preparation which is broadly comparable, having antibacterial and ､ ･ ｾ ･ ｲ ｧ ･ ｮ ｴ activity, and which is well known to have some effectiveness in the treatment of acne. These two preparations were used alternately for six weeks each, the first to be used being randomly selected.
We are inclined to think that for a short-term assessment the best that can be decided is: Much improved; improved; unchanged; and that numerical scores give an appearance of statistical accuracy which is in fact spurious. Both the new application under trial and the control could be expected to produce some improvement in a proportion of cases, and for this reason we attached chief importance to a comparison of the gel with the control, rather than attempting to add up numerical scores.

THE PATIENTS
All patients presenting with active acne were included in the trial with the sole exception of those who had recently started tetracycline treatment. All cases were examined by the same doctor. After six weeks they were re-assessed and the application changed to the alternative. They were finally assessed by the same doctor after the second six-week ｰ ･ ｲ ｩ ｯ ｾ Ｎ A few were seen more often if the occasion demanded; this was usually because of possible irritant effects, either because the patient anticipated them, or because they actually occurred.
Patients were told that these were new products, and that they would be asked to give their judgement as to their effectiveness and acceptability, and eventually to express a preference for one or the other. They were instructed toapply the material to the affected area after wetting the skin. This was worked into a lather with the fingers for at least one minute and then rinsed off with water. Particularly bad spots were to be dabbed with the undiluted product and rubbed in. Although the two products were clearly different in appearance, the patient was not told which was the one under test and which was the control.
A record was kept ofthe severity ofthe acne and of changes during the six-week periods, of irritant effects, as observed by the physician and as reported by the patient.

RESULTS
34 patients started the trial. One developed a reaction after three days which was thought by the doctor to be sunburn, but by the patient to be due to the application. This patient did not proceed with the trial. Of the remaining 33, five did not complete the trial, for reasons unknown. Of the 28 who completed the trial. the severity of their acne was rated as: r ns BRITISH JOURNAL. OF CLIN ICAL PRACTICE Slm:-EFJ<'ECTS Eleven patients mentioned side-effects from the gel and nine from the control. These were mainly in the form of a slightly drying effect, the skin feeling a little tight or scaling and occasionally with slight itching. In two cases. redness and soreness led the patient to discontinue treatment with the gel and in three cases with the control. All these symptoms were thought to result from the cleansing and degreasing action of the materials. SUMMARY A local application. in the form of a gel. has been developed for the treatment of acne. It combines surface activity with anti-bacterial and antilipase action.
Clinical trial has shown it to produce improvement in about two-thirds of cases. and to be preferred to a control application of proven efficacy.